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. 2023 May 26;23(1):478.
doi: 10.1186/s12885-023-10958-4.

ARL4C is associated with epithelial-to-mesenchymal transition in colorectal cancer

Ryo Kanai  1 , Takeshi Uehara  2 , Takahiro Yoshizawa  3 , Masato Kamakura  4 , Tomoyuki Nakajima  1 , Yasuhiro Kinugawa  1 , Mai Iwaya  1 , Shiho Asaka  1 , Masato Kitazawa  3 , Tadanobu Nagaya  4 , Hiroyoshi Ota  1   5
Affiliations

ARL4C is associated with epithelial-to-mesenchymal transition in colorectal cancer

Ryo Kanai et al. BMC Cancer. .

Abstract

Background: ADP-ribosylation factor-like protein 4 C (ARL4C) is a member of the ARF small GTP-binding protein subfamily. The ARL4C gene is highly expressed in colorectal cancer (CRC). ARL4C protein promotes cell motility, invasion, and proliferation.

Methods: We investigated the characteristics of ARL4C by comparing its expression at the invasion front and relationships with clinicopathological data using RNAscope, a highly sensitive RNA in situ method.

Results: In all cases, ARL4C expression was observed in cancer stromal cells and cancer cells. ARL4C expression in cancer cells was localized at the invasion front. In cancer stromal cells, ARL4C expression was significantly stronger in cases with high-grade tumor budding than in cases with low-grade tumor budding (P = 0.0002). Additionally, ARL4C expression was significantly increased in patients with high histological grade compared with those with low histological grade (P = 0.0227). Furthermore, ARL4C expression was significantly stronger in lesions with the epithelial-to-mesenchymal transition (EMT) phenotype compared with the non-EMT phenotype (P = 0.0289). In CRC cells, ARL4C expression was significantly stronger in cells that had the EMT phenotype compared with those with a non-EMT phenotype (P = 0.0366). ARL4C expression was significantly higher in cancer stromal cells than in CRC cells (P < 0.0001).

Conclusion: Our analysis reinforces the possibility that ARL4C expression worsens the prognosis of patients with CRC. Further elucidation of the function of ARL4C is desired.

Keywords: ARL4C; Colorectal adenocarcinoma; Colorectal cancer; RNA in situ hybridization; Tumor budding.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
ARL4C expression. Representative features of higher ARL4C expression in cancer stromal cells (A and B). Detailed images of ARL4C-positive dots are shown in the insert image in B. Representative features of lower ARL4C expression (C and D). Detailed images of ARL4C-positive dots (arrows) are shown in the insert image in D. (A and C, hematoxylin eosin; B and C, ARL4C).
Fig. 2
Fig. 2
ARL4C expression in cancer stromal cells in the tumor budding (TB) region. Representative features of cases with higher TB grade and higher ARL4C expression (A and B). Detailed images of ARL4C-positive dots are shown in the insert image in B. (A, hematoxylin eosin; B, ARL4C).
Fig. 3
Fig. 3
Box plot of ARL4C expression scores in cancer stromal cells and cancer cells. ARL4C scores were significantly higher in cancer stromal cells than in cancer cells (P < 0.0001)
See this image and copyright information in PMC

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